Related Experiment Video

Updated: Nov 20, 2025

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Published on: May 2, 2018

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Carbapenem Use Is Driving the Evolution of Imipenemase 1 Variants

Zishuo Cheng1, Christopher R Bethel2, Pei W Thomas3

  • 1Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA.

Antimicrobial Agents and Chemotherapy
|January 20, 2021
PubMed

Insights

Metallo-β-lactamases (MBLs) are a growing threat, with IMP variants showing increased carbapenem resistance. Their evolution is driven by distinct selective pressures, unlike other MBLs.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Metallo-β-lactamases (MBLs) pose a significant clinical challenge due to their ability to neutralize β-lactam antibiotics.
  • No inhibitors for MBLs are currently available, and numerous variants have emerged within MBL subfamilies.

Purpose of the Study:

  • To investigate the evolution of imipenemase (IMP) genes (blaIMP) and their clinical implications.
  • To understand the molecular mechanisms behind increased antibiotic resistance in IMP variants.

Main Methods:

  • Site-directed mutagenesis was used to generate 20 clinically derived IMP-1 like variants in Escherichia coli DH10B.
  • Biochemical, biophysical, and molecular modeling studies were performed to compare key IMP variants (IMP-1, IMP-6, IMP-10, IMP-78).
  • Minimum inhibitory concentration (MIC) values were assessed for various IMP variants.

Main Results:

  • IMP-1 like variants with S262G or V67F substitutions demonstrated enhanced resistance to carbapenems and reduced resistance to ampicillin.
  • The IMP-78 (S262G/V67F) variant exhibited the most substantial changes in MIC values compared to IMP-1.
  • Unlike NDM and VIM variants, IMP-1 like variants did not provide a survival advantage under limited zinc conditions.

Conclusions:

  • The evolution of IMP-6, IMP-10, and IMP-78 variants is influenced by unique selective pressures.
  • Understanding these evolutionary dynamics is crucial for developing strategies against MBL-mediated antibiotic resistance.
Keywords:
IMPS262GV67Fbeta-lactamasecarbapenemasecarbapenemsimipenemase

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